1. Admission and discharge criteria for children who are6–59 months of age with severe acute malnutritionAdmission criteria for children who are 6 to 59 months of age with severeacute malnutritionPopulation:Children with severe acute malnutrition:

Children who are more than 6 months of age with a weight for height <–2 Z-score, or Children who are 6–59 months of age, with a mid-upper arm circumference <125 mm Urban/rural Camp/no camps Oedema/no oedema Prevalence of oedema Emergency/non-emergency Community/health-care facilities Active screening/passive screening. HIV/TB prevalence HIV/TB individual status

Intervention: Standard treatment targeting children with low mid-upper arm circumference

Control: Standard treatment targeting children with low weight-for-height

Outcomes: Response to treatment assessed by standard outcome for severe and moderate acute malnutrition

Settings: Programmatic setting in populations with moderate acute malnutrition prevalence >5%

Discharge criteria for children who are 6–59 months of age with severeacute malnutritionPopulation:Children above 6 months of age with severe acute malnutrition:

HIV positive/HIV negative/unknown HIV-endemic settings/non-HIV-endemic settings

Intervention: For programme using mid-upper arm circumference: mid-upper arm circumference ≥125 mm or any

other discharge criteriaControl:

For programme using mid-upper arm circumference: weight gain of 15–20% after oedemadisappears

For programme using weight-for-height: weight-for-height >–11 standard deviation or weight gain of 15–20% after oedema disappears.

Outcomes:1. Mortality2. Relapse3. Adverse effects4. Cost of treatment per child treatedSettings:

All settings

2. Where to manage children with severe acute malnutritionwho have oedemaPopulation:Children who are above 6 months of age with severe acute malnutrition:

Oedema +/oedema++/oedema +++/no oedemaIntervention:

Good appetite or no medical complications and oedema +/oedema++ Marasmic kwashiorkor Children who are above 6 months of age and <4 kg

Control: Good appetite or no medical complications as outpatient

Outcomes:1. Short-term mortality2. Recovery rate3. Time to recover4. Weight gain5. Use of resources6. Adverse effects7. Length gainSettings:

Outpatient

3. Use of antibiotics in the management of children withsevere acute malnutrition in outpatient carePopulation:Children who are under 5 years of age with severe acute malnutrition:

HIV positive/HIV negative/unknown HIV-endemic settings/non-HIV-endemic settings Under 6 months/above 6 months of age Clinical signs of infection (to be defined)/no clinical signs of infection Local sensitivity

Intervention: Amoxicillin, ampicillin, cephalosporin, chloramphenicol, ciprofloxacin co-trimoxazole, gentamicin,

metronidazoleControl:

No antibiotics, or Different antibiotics

Outcomes:1. Mortality rate2. Recovery rate3. Adverse effects; relapse4. Time to recover; weight gainSettings:

Low-resource countries

4. Vitamin A supplementation in the treatment of children

with severe acute malnutritionEffectiveness and safety of vitamin A supplementation in children withsevere acute malnutritionPopulation:Children who are under 5 years of age with severe acute malnutrition:

Presence of oedema/no presence of oedema Presence of eye signs/no eye signs HIV positive/HIV negative/unknown HIV-endemic settings/non-HIV-endemic settings Prevalence of vitamin a deficiency in the population (+/– other sources of vitamin A, as national/local programmes of supplementation/fortification of

vitamin A) Under 6 months/above 6 months of age Measles diagnosis (outbreak)

Intervention:Vitamin A single mega dose:

Admission/rehabilitation/dischargeControl:

Daily low doses (including therapeutic foods)Outcomes:1. Mortality rate2. Adverse effects (to be specified); morbidity3. Recovery rate4. Relapse5. Time to recover; weight gainSettings:

Low-resource countries

5. Therapeutic feeding approaches in the management ofsevere acute malnutrition in children who are6–59 months of ageFeeding outpatient children with severe acute malnutrition and diarrhoeaPopulation:Children who are under 5 years of age with severe acute malnutrition and diarrhoea, defined as:

Diarrhoea based on the mother recall or other definitions With vomiting/without vomiting Presence of oedema/no presence of oedema Under 6 months/above 6 months of age Persistent diarrhoea defined as more than 2 weeks HIV positive/HIV negative/unknown HIV-endemic settings/non-HIV-endemic settings Breastfed/ non-breastfed

Intervention: Other foods

Control: Ready-to-use therapeutic food

Outcomes:

1. Referral to hospitals2. Recovery from diarrhoea3. Adverse effects4. Time to recover from diarrhoeaSettings:

OutpatientFeeding inpatient children with severe acute malnutrition and diarrhoeaPopulation:Children who are 5 years of age with severe acute malnutrition and diarrhoea, defined as:

Diarrhoea based on the mother recall or other definitions With vomiting/without vomiting Presence of oedema/no presence of oedema Under 6 months/above 6 months of age Persistent diarrhoea defined as more than 2 weeks HIV positive/HIV negative/unknown HIV-endemic settings/non-HIV-endemic settings Breastfed/ non-breastfed

Intervention: Other recipes (e.g. lactose-free F-75 formulation)

Control: Cooked cereal-based F-75 or glucose-polymer-based F-75

Outcomes:1. Use of intravenous fluids2. Recovery from diarrhoea; duration of diarrhoea3. Adverse effectsSettings:

InpatientFeeding children with severe acute malnutrition in the transition phasePopulation:Children who are 6–59 months of age with severe acute malnutrition and return of appetite andmost/all oedema disappeared:

Presence of oedema/no presence of oedema on admission HIV positive/HIV negative/unknown HIV-endemic settings/non-HIV-endemic settings

Intervention: Combination of F-75/ready-to-use therapeutic food with/without energy restriction, or F-100/

ready-to-use therapeutic food with/without energy restriction, or F-100 without energyrestriction, or ready-to-use therapeutic food with/without energy restrictionControl:

F-100: 130 mL/kg/day increasing 10 mL/kg/ feed if eaten until drinking 200 mL/kg/dayOutcomes:1. Mortality rate; recovery rate2. Cardiac embarrassment3. Adverse effect (refeeding syndrome)4. RelapseSettings:

Inpatient

6. Fluid management of children with severe acute

malnutritionManagement of dehydration without shock due to diarrhoea (and vomiting)in children with severe acute malnutritionPopulation:Children who are 5 years of age with severe acute malnutrition:

Dehydration based on the mother recall of watery diarrhoea or other definitions With vomiting/without vomiting Presence of oedema/no presence of oedema Under 6 months/above 6 months of age Severe watery diarrhoea without signs of shock (e.g. cholera) or hyponatraemia

Intervention:Treatment with different rehydration solutions:

Oral/parenteral/other (F-75/breastfeeding)Control:

Treatment with ReSoMalOutcomes:1. Use of intravenous fluids2. Recovery from dehydration3. Time to recover from dehydration4. Adverse effects (convulsions, hyponatraemia, oedema, cardiac embarrassment, shock)Settings:

All settingsManagement of shock with intravenous fluids in children with severeacute malnutritionPopulation:Children who are under 5 years of age with severe acute malnutrition and shock:n By definition of shock, as:— Lethargy or unconsciousness and cold hands plus either slow capillary refill or weak or fastpulse— Cold hands with capillary refill longer than 3 s and weak and fast pulse— Other definitions including signs of possible septic shock

Presence of oedema/no presence of oedema Under 6 months/above 6 months of age

Intervention:Treatment with isotonic fluids, colloids fluids or crystalloid fluids:

Quantity/kg/child Speed Monitoring: frequent/other schemes

Control: Treatment with hypotonic fluids as in current guidelines (1)

Outcomes:1. Case-fatality rate2. Recovery from shock3. Adverse effects (convulsions, hyponatraemia, hypokalaemia, oedema, cardiac embarrassment)4. Time to recover from shockSettings:

All settingsBlood or plasma transfusion in children with shock after failure ofintravenous fluid in children with severe acute malnutrition

Population:Children who are under 5 years of age with severe acute malnutrition not responding to intravenousfluid treatment of shock:

By definition of shock, as:— Lethargy or unconsciousness and cold hands plus either slow capillary refill or weak or fastpulse— Cold hands with capillary refill longer than 3 s and weak and fast pulse— Other definitions including signs of possible septic shock

Presence of oedema/no presence of oedema Under 6 months/above 6 months of age

Intervention:Treatment with blood or plasma transfusion:

Quantity/kg/child Speed

Control: No blood transfusion

Outcomes:1. Case-fatality rate2. Recovery from shock3. Adverse effects (convulsions, hyponatraemia, oedema, cardiac embarrassment)4. Time to recover from shockSettings:

All settings

7. Management of HIV-infected children with severeacute malnutritionWhat are the implications of severe acute malnutrition on antiretroviral drugtreatment initiation and dosing?In children who are 0–59 months of age with severe acute malnutrition, atwhich stage in nutritional recovery should antiretroviral drug treatment becommenced?Population:Children who are 0–14 years of age with severe acute malnutrition:

Subgroups:— Age <6 months, age 6 months to 5 years— Oedema, no oedema— TB status: positive/negative/unknownIntervention:

Start nutritional therapy plus antiretroviral drug treatment concurrentlyControl:

Start nutritional therapy and withhold antiretroviral drug treatment for 1 week/2 weeks (within stabilization phase)

Start nutritional therapy and withhold antiretroviral drug treatment until rehabilitation phaseOutcomes:1. Mortality2. Markers of nutritional status: lean body mass, height gain, body weight, weight-for-height,weight-for-age, body mass index, mid-upper arm circumference3. Improvements in CD4 %, CD4 counts, viral load; tolerance of antiretroviral drug treatment

(adverse effects)4. Adherence to antiretroviral drug treatmentTiming:

From time of initiation of services to first 6 months of treatmentIn children with HIV and severe acute malnutrition should antiretroviral drugtreatment dosing be adjusted from doses for non-malnourished children?Population:Children who are 0–59 months of age with severe acute malnutrition:

Subgroups:— Age <6 months, age 6 months to 5 years— Oedema, no oedema— TB status: positive/negative/unknownIntervention:

antiretroviral drug treatmentComparator:

Compare standard antiretroviral drug treatment doses between children with and withoutsevere acute malnutrition of the same weight

Compare antiretroviral drug treatment pharmacokinetics (peak levels, clearance) betweenchildren of the same age with and without severe acute malnutrition, with weight-appropriate dosesOutcomes:1. Antiretroviral drug treatment tolerance/adverse events2. Mortality3. Measures of pharmokinetics4. Measures of antiretroviral drug treatment absorption5. Markers of nutritional status: body weight, weight-for-height, weight-for-age, body mass index,mid-upper arm circumference6. Change in CD4 countsTiming:

During the first 3 months of antiretroviral drug treatment

8. Identifying and managing infants who are less than 6months of age with severe acute malnutritionAdmission and discharge criteria for infants who are less than 6 months ofage with severe acute malnutritionPopulation:Children who are less than 6 months of age with severe acute malnutrition:

Oedema/no oedema 0–2 months/2–6 months HIV positive/HIV negative/unknown HIV-endemic settings/non-HIV-endemic settings

Intervention: Admission criteria: mid-upper arm circumference, chest circumference, head circumference, weight

loss, breastfeeding failure, weight-for-length different cut-off values Discharge criteria: criteria different from those specified for control

Control: Admission criteria: weight-for-length <–3 standard deviations or visible severe wasting (given the lack

of gold standard it is advised to compare different criteria) Discharge criteria: there is no standard for this age group; the general recommendation is:

— for programme using mid-upper arm circumference: weight gain of 15–20% after oedemadisappears— for programme using weight-for-height: weight-for-height >–1 standard deviation or weightgain of 15–20% after oedema disappearsOutcomes:1. Short-term mortality2. Recovery rate; weight gain3. Adverse effects4. Time to recover5. Use of resources6. Excessive use of breast milk substitute; length gainRestoration of successful exclusive breastfeeding (added later, not included in the ranking exercise)Settings:

InpatientFeeding severely malnourished infants who are less than 6 months of age(breastfed or non-breastfed infants)Population:Infants less than 6 months of age:

0–2 months/2–6 months Access to breast milk/no access to breast milk Stabilization/rehabilitation Presence of oedema/no oedema HIV positive/HIV negative/unknown HIV-endemic settings/non-HIV-endemic settings

Intervention: Different formulation of F-75 (initiation of treatment), breast milk substitute, breast milk substitute

specific for premature infants, F-100, F-100 diluted, expressed breast milk, animal milk Supplementary suckling method/cup feeding

Control: Breast milk if accessible, if not, breast milk substitute

Outcomes:1. Mortality2. Recovery rate; weight gain3. Diarrhoea4. Restoration of successful exclusive breastfeeding5. Time to recover6. Length gain7. Adverse effects8. Breast milk outputSettings:

Inpatient